Choi and Kim's research examines delivering drugs at the nanoscale

5/2/2015

Ashish Valentine, ECE ILLINOIS

In his office at the ECE building, Professor Kyekyoon Kim shows off a picture of semi-spherical objects that look almost like soccer balls. They can be blocky or spherical, but are actually 1,000 times smaller than the width of a human hair.

These particles (blue), thousands of times smaller than a human hair, could hold the key to solving a host of medical issues, from improving vaccines to treating cancer.
These particles (blue), thousands of times smaller than a human hair, could hold the key to solving a host of medical issues, from improving vaccines to treating cancer.

These are precision nanoparticles, and Kim, with senior research scientist and lecturer Hyungsoo Choi, has been researching them for the last 20 years. They, along with precision micro-spheres and capsules, could solve a host of medical issues in the human body, from treating cancer to simplifying multi-stage vaccinations. By carrying therapeutics to specific parts of the body and being absorbed by cells, the precision particles could target diseases like cancer and even reverse strokes.

The downside to nanoparticles: several scientists have raised concerns about their toxicity. Cells engulf nanoparticles in the same way as they eat any other naturally occurring molecules as part of the body’s normal functions. Sometimes, once engulfed, these nanoparticles can linger inside cells, disrupting internal functions.

The journal Nanomedicine published a paper co-written by Kim and Choi, along with their students Elizabeth Joachim and Inyong Kim. It thoroughly examines the reality of this threat and how it affects different types of cells. Inyong Kim was the paper’s lead author.

The paper documented the team’s findings, which found the chances of nanoparticle being eaten by a cell depend on the size and dose of the nanoparticle, and on the type of cell consuming it. A lung cell, for example, could absorb just the right amount of the same nanoparticles that would break down a skin cell from the inside.

Transmission electron micrograph of A549 human lung epithelial cells incubated for 24 hours at 200 ug/ml doses with 60 nm SNPs (silicon nanoparticles) showing cell morphology and cytoplasmic texture. Inset shows scanning electron micrograph of the corresponding SNPs.
Transmission electron micrograph of A549 human lung epithelial cells incubated for 24 hours at 200 ug/ml doses with 60 nm SNPs (silicon nanoparticles) showing cell morphology and cytoplasmic texture. Inset shows scanning electron micrograph of the corresponding SNPs.

This research results in a much more nuanced view of nanoparticles, in which the size of the particle determines what types of cells take it in. This conclusion points at several applications of differently sized nanoparticles, depending on what conditions scientists want to treat in the body.

“Nanoparticles of an optimal size are less toxic at low doses, but more toxic at high doses due to their enhanced cellular uptake,” Choi said. “These findings on the size and dose dependent toxicity may provide a practical guideline for designing a nanoparticle-mediated drug delivery system. For targeted cancer treatments, employing the optimal-sized particles as a drug carrier would be even more beneficial.”

Hyungsoo Choi
Hyungsoo Choi

Choi and Kim’s precision particles, both at the nano- and micro-scale, are also constructed from biodegradable materials, though the specific composition of the particle can be customized depending on how long it needs to linger in the body. Many vaccines, Kim mentioned, need to be given to patients in multiple stages. The current vaccine for anthrax, for example, needs to be given multiple times: the first two inoculations are two weeks apart, the next one is four weeks afterward, then the last is a whole three months later.

Though this system is inconvenient but workable for most of us, Kim emphasized that it fails anyone that can’t afford to keep coming back for vaccinations, such as soldiers deployed in combat zones who need the vaccine to protect against biological warfare.

“Imagine, in the chaos of the battlefield, a soldier has to come back and get vaccinated regularly,” Kim said. “Not to mention, soldiers could be exposed to anthrax in the field in the middle of vaccination periods, rendering it useless.”

Kyekyoon Kim
Kyekyoon Kim

Instead, a single shot of an assortment of microcapsules could be administered to the soldier, and the particles would be designed to biodegrade at the specific times that vaccines need to be administered.   

Choi and Kim have also found a way to use their nanoparticles to reverse strokes in lab tests, and believe their method could eventually target the human brain as well. Most drugs are blocked from reaching the brain by a structure called the blood-brain barrier: a network of cells that only allows nanoparticles smaller than several nanometers across to enter the brain.

Though most particles are too large to pass this barrier, Kim and Choi have demonstrated an alternate way to deliver them to the brain through the nose. In animal tests, a nanoparticle treatment administered through the nose could reverse strokes up to six hours after they occurred.

The results of Choi and Kim’s research on toxicity push them forward, as they show how effective and targeted nanoparticles can be when they’re properly tailored to a disease.

“The work we’ve done has shown us just how effective tailored high-precision particles can be,” Kim said. “There are a number of ways our research can translate out into solving critical medical problems. When students enter electrical engineering, they hardly expect to be looking into things like this. That’s why I tell them the abbreviation EE actually stands for Everything Exciting: start with a degree here and you can go on to do all kinds of amazing things.”